HPV DNA Detection Research Articles

Protease inhibitor effects on prevalence of bacterial vaginosis and human papillomavirus-related lesions.

Antiretrovirals of the protease inhibitor (PI) class tend to achieve low concentrations in biological fluids. This study aimed to analyze possible changes in the vaginal microbiome and frequency of cervical human papillomavirus (HPV)-DNA and HPV-related lesions associated with the use of PI in antiretroviral therapy (ART). Eighty-eight women with human immunodeficiency virus infection were divided in two groups: ART with PI and without PI. All the participants underwent anamnesis with demographic data collection. The total DNA, used as the template in the polymerase chain reaction-based assays for the detection of HPV-DNA, was extracted from cervical samples during cervical cytopathology. There were no differences between the groups with respect to HPV-related lesions. Despite the higher prevalence of bacterial vaginosis (BV) in the PI group (33.96% vs 17.14%), the difference was insignificant when considering all women (P = 0.066). When women with a detectable viral load and a CD4+ T-cell count <200 were excluded in both groups, BV was found to be more prevalent in the PI group (odds ratio, 3.349; 95% confidence interval, 1.113-11.41, P = 0.049). No associations were found between BV and age, condom use, cervical HPV, time with current ART regimen, unprotected receptive anal intercourse and cervical HPV-related lesions. The use of PI did not alter the frequencies of HPV-DNA and HPV-related lesions. However, an increased frequency of BV was found in women using PI after excluding women with a detectable viral load and a CD4+ T-cell count of <200.

Review Article: Molecular Diagnosis of Human Papilloma Virus Infection

Abstract Infection with human papillomaviruses (HPVs) can cause warts on cutaneous epithelium, while in the anogenital region these viruses can cause both genital warts and various forms of cancer in men and women. The main interest in HPV relates to its causative role in cervical cancer. Most HPV infections in young women resolve spontaneously, most frequently within a 24-month period. Identification of HPV genotypes would require the use of type-specific probes in multiple in situ hybridization experiments. Alternatively, HPV-DNA can be directly isolated from clinical samples and detected by Southern blot or dot spot hybridization. However, such approaches are insensitive, labor intensive and unsuitable for high through put screening. Therefore, nucleic acid amplification methods have been developed to increase the sensitivity as well as the specificity of HPV-DNA detection.

Role of Platelets, Bacterial Vaginosis, Serum Interleukinsand TNF In Genital Human Papillomavirus InfectionAmong Black Female Population in Nigeria

The study was aimed at evaluating the relationship between platelets count, bacterial vaginosis and immune response in cervical human Papillomavirus positive women in Bayelsa State. Cervical smears were collected from apparently healthy subjects attending clinics in Bayelsa State. Consensus primers GP5+/6+ and MY09/11 were used to detect HPV DNA in cervical smears and further subjected to multiplex PCR for molecular typing of HPV subtypes. Nugent method was used for scoring of bacterial vaginoses based on gram staining reaction. Interleukins were studied using sandwich ELISA kits. The prevalence of bacterial vaginosis among HPV positive, HPV negative and high-risk HPV was 35.9% and 18.2% and 51.7% respectively. Bacterial vaginosis expressed statistically significant relationship with high risk HPV (OR=9.64, P=0.002, 95%CI= 1.08-86.26).Interleukin 4 (IL-4), IL-6, IL-8, IL-10, IL-12, IL-17, IL-18, Tumor Necrotic Factor (TNF) and Interferon Gamma (INF-γ) were equally higher in HPV positive participants compared with negative participants and statistically significant.

Extracapsular extension of neck nodes and absence of human papillomavirus 16-DNA are predictors of impaired survival in p16-positive oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV-negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV-driven disease. In p16-negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16-positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16-positive OPSCC. In a cohort of 92 patients with p16-positive, lymph node (N)-positive (stage III-IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16-positive/HPV16 DNA-positive, 62 of 92 (67%) were ECE-positive, and 45 of 62 (72.6%) were ECE-positive, p16-positive, and HPV16 DNA-positive. Differences in outcome were assessed using Kaplan-Meier plots and Cox proportional hazard regression (CoxR) for tumor-specific survival and overall survival (OS). The mean numbers of positive lymph nodes in ECE-positive patients (5.0 positive lymph nodes; 95% CI, 3.8-6.4 positive lymph nodes) and ECE-negative patients (2.4 positive lymph nodes; 95% CI, 1.8-2.9 positive lymph nodes) were different (P=.0007). ECE affected OS and tumor-specific survival in p16-positive patients (P=.007 and P=.047, respectively) and in p16-positive/HPV16 DNA-positive patients (P=.013 and P=.026, respectively). Related to the unequal distributions of ECE-positive/HPV16 DNA-negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45months, respectively; median OS, 64.7months, not reached, and 41.1months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16-positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17-9.89; P=.025) and even greater impaired OS in those with p16-positive/HPV16 DNA-positive OPSCC (HR, 8.64; 95% CI, 1.12-66.40; P=.038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors. ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16-positive OPSCC because several lines of evidence demonstrate their impact on survival.

Human Papillomavirus and Factors Associated with Recurrence in Sinonasal Inverted Papillomas from Poland and Spain.

Sinonasal inverted papilloma (SNIP) is a benign but locally aggressive tumor that has a tendency for recurrence and malignant transformation. The role of human papillomavirus (HPV) in SNIP is controversial. To determine the HPV-DNA prevalence and type distribution in SNIP in two different geographic areas and assess the association between SNIP recurrence and HPV infection, as well as additional potential etiologic factors. Two retrospective cohorts of SNIP patients from Poland and Spain were evaluated. Demographic, tobacco/alcohol use, clinical, and follow-up data were collected. All samples were subject to histopathologic evaluation, DNA quality control, and HPV-DNA detection by PCR. HPV-DNA positive samples and a random sample of HPV-DNA negative cases were further subject to p16INK4a analysis. Proportional-hazards models were used to evaluate the risk of recurrence by selected variables. Seventy-nine SNIP patients (46 from Spain diagnosed between 1995 and 2014, and 33 from Poland diagnosed between 2012 and 2017) were included in the study. HPV-DNA was detected in four patients (5.1%), two from each region, and all four were positive for the HPV11 subtype. Seventeen patients (21.5%) experienced recurrence, with a median time to recurrence of 14months. No association was identified between lesional HPV-DNA positivity, toxic habits, Krouse stage, or malignant transformation and a higher risk of recurrence. The low prevalence of HPV-DNA in SNIPs suggests that HPV is not a main etiology for development of these lesions. With a lack of association between the evaluated factors and recurrence, further research with larger number of patients and additional biomarkers is warranted to further understand predisposing risk factors.

Assessment of clinical performance of an ultrasensitive nanowire assay for detecting human papillomavirus DNA in urine

ObjectiveTo evaluate whether HPV DNA in urine has potential advantages as an alternative biomarker for HPV-based cervical cancer screening. MethodsAmong patients with Cobas HPV test results, a total of 67 HPV-positive (n = 42) and -negative (n = 25) women who agreed to participate in this study were willing to provide paired cervical and urine samples, and we observed concordance between sample types from each patient in identifying HPV genotypes using the nanowire assay. ResultsWe detected high-risk strains of HPV DNA in unprocessed urine specimens using polyethyleneimine-conjugated nanowires (PEI-NWs). Concordance for high-risk HPV (hrHPV) between paired urine and cervical samples was 90.4% (κ = 0.90; 95% CI: 0.80–100.00). The virological sensitivity and specificity for detection of HPV DNA from a small urine sample (200 μL) were 81.3% (κ = 0.83; 95% CI: 62.1–100.0) and 98.0% (κ = 0.83; 95% CI: 94.2–100.0) for HPV16 group, 100.0% (κ = 0.65; 95% CI: 100.0–100.0) and 95.3% (κ = 0.65; 95% CI: 90.1–100.0) for HPV18 group, and 96.4% (κ = 0.97; 95% CI: 89.6–100.0) and 100.0% (κ = 0.97; 95% CI: 100.0–100.0) for other hrHPV group, respectively. ConclusionsThe nanowire assay demonstrated excellent ability to identify HPV DNA from urine specimens. We observed an excellent agreement in the detection of high-risk HPV between paired urine and cervical samples, even with small urine sample volume.

Rational genomic optimization of DNA detection for human papillomavirus type 16 in head and neck squamous cell carcinoma.

We aimed to use genomic data for optimizing polymerase chain reaction (PCR) primer/probe sets for detection of human papillomavirus (HPV)-16 in body fluids of patients with HPV-related head and neck squamous cell carcinoma (HPV-HNSCC). We used genomic HPV-HNSCC sequencing data from a single institutional and a TCGA cohort. Optimized primer/probe sets were designed and tested for analytical performance in CaSki HPV-16 genome and confirmed in salivary rinse samples from patients with HPV-HNSCC. The highest read density was observed between E5 and L2 regions. The E1 region contained a region that was universally present. Among candidate PCR primer/probe sets created, six reliably detected 30 HPV-16 copy number. In a CLIA certified laboratory setting, the combination of two novel primer/probe with E7 sets improved performance in salivary rinse samples with a sensitivity of 96% and specificity of 100%. PCR-based detection of HPV-16 DNA in HPV-HNSCC can be improved using rational genomic design.

Acoustofluidic Salivary Exosome Isolation: A Liquid Biopsy Compatible Approach for Human Papillomavirus–Associated Oropharyngeal Cancer Detection

Previous efforts to evaluate the detection of human papilloma viral (HPV) DNA in whole saliva as a diagnostic measure for HPV-associated oropharyngeal cancer (HPV-OPC) have not shown sufficient clinical performance. We hypothesize that salivary exosomes are packaged with HPV-associated biomarkers, and efficient enrichment of salivary exosomes through isolation can enhance diagnostic and prognostic performance for HPV-OPC. In this study, an acoustofluidic (the fusion of acoustics and microfluidics) platform was developed to perform size-based isolation of salivary exosomes. These data showed that this platform is capable of consistently isolating exosomes from saliva samples, regardless of viscosity variation and collection method. Compared with the current gold standard, differential centrifugation, droplet digital RT-PCR analysis showed that the average yield of salivary exosomal small RNA from the acoustofluidic platform is 15 times higher. With this high-yield exosome isolation platform, we show that HPV16 DNA could be detected in isolated exosomes from the saliva of HPV-associated OPC patients at 80% concordance with tissues/biopsies positive for HPV16. Overall, these data demonstrated that the acoustofluidic platform can achieve high-purity and high-yield salivary exosome isolation for downstream salivary exosome-based liquid biopsy applications. Additionally, HPV16 DNA sequences in HPV-OPC patients are packaged in salivary exosomes and their isolation will enhance the detection of HPV16 DNA.

Human papillomavirus genotypes and P16INK4A expression in squamous penile carcinoma in Mexican patients

BackgroundApproximately 50% of cases of penile carcinoma (PeCa), a rare neoplasm worldwide, are associated with human papillomavirus (HPV). However, the detection of HPV-DNA is not sufficient to consider it the etiological factor in the development of this type of cancer. Currently, the overexpression of P16INK4A is used as a surrogate biomarker of HPV carcinogenesis. Information on PeCa in Mexico is scarce, particularly regarding cases related to HPV and genotype frequency.ObjectiveTo evaluate the presence of HPV, its genotypes, and the presence of multiple genotypes, and the expression of P16INK4A, as well as its clinical and histopathological parameters.MethodsFor HPV-DNA detection and P16INK4A expression, we used the INNO-LiPA® test and immunohistochemistry, respectively.ResultsSixty cases of PeCa were evaluated, of which 75% were HPV-non-related histological variants. We found that 58.9% (33/56) of PeCa cases were HPV-DNA positive, while 30.9% of the cases evaluated (17/55) were positive for P16INK4A. HPV16 was the main genotype in 42.9% of the cases, followed by HPV52 in 7.1% and HPV18 in 5.4%. Within the HPV-positive cases, 27.3% had multiple genotypes. All HPV-positive patients under the age of 45 years were positive only for HPV16.ConclusionsHPV16 was the most commonly detected genotype in PeCa. HPV 31, 35 and 39 were infrequent; however, they were related to a single infection and P16INK4A overexpression; thus, they seem to be relevant in PeCa carcinogenesis. Our results suggest that P16INK4A overexpression could be useful for the classification of HPV-related PeCa. The role of multiple HPV genotypes in the development and prognosis of PeCa is still not completely understood. Thus, it is necessary to define criteria to establish reliable ways to classify HPV-related PeCa that could lead to optimal therapeutic approaches.

Introduction of primary screening using high-risk HPV DNA detection in the Dutch cervical cancer screening programme: a population-based cohort study

BackgroundIn January 2017, the Dutch cervical cancer screening programme transitioned from cytomorphological to primary high-risk HPV (hrHPV) DNA screening, including the introduction of self-sampling, for women aged between 30 and 60 years. The Netherlands was the first country to switch to hrHPV screening at the national level. We investigated the health impact of this transition by comparing performance indicators from the new hrHPV-based programme with the previous cytology-based programme.MethodsWe obtained data from the Dutch nationwide network and registry of histo- and cytopathology (PALGA) for 454,573 women eligible for screening in 2017 who participated in the hrHPV-based programme between 1 January 2017 and 30 June 2018 (maximum follow-up of almost 21 months) and for 483,146 women eligible for screening in 2015 who participated in the cytology-based programme between 1 January 2015 and 31 March 2016 (maximum follow-up of 40 months). We compared indicators of participation (participation rate), referral (screen positivity; referral rate) and detection (cervical intraepithelial neoplasia (CIN) detection; number of referrals per detected CIN lesion).ResultsParticipation in the hrHPV-based programme was significantly lower than that in the cytology-based programme (61% vs 64%). Screen positivity and direct referral rates were significantly higher in the hrHPV-based programme (positivity rate: 5% vs 9%; referral rate: 1% vs 3%). CIN2+ detection increased from 11 to 14 per 1000 women screened. Overall, approximately 2.2 times more clinical irrelevant findings (i.e. ≤CIN1) were found in the hrHPV-based programme, compared with approximately 1·3 times more clinically relevant findings (i.e. CIN2+); this difference was mostly due to a national policy change recommending colposcopy, rather than observation, of hrHPV-positive, ASC-US/LSIL results in the hrHPV-based programme.ConclusionsThis is the first time that comprehensive results of nationwide implementation of hrHPV-based screening have been reported using high-quality data with a long follow-up. We have shown that both benefits and potential harms are higher in one screening round of a well-implemented hrHPV-based screening programme than in an established cytology-based programme. Lower participation in the new hrHPV programme may be due to factors such as invitation policy changes and the phased roll-out of the new programme. Our findings add further to evidence from trials and modelling studies on the effectiveness of hrHPV-based screening.

A fluorometric hybridization assay for detecting and genotyping high-risk human papillomavirus 16 and 18 in archival tissues of cervical specimens.

Early diagnosis and genotyping of high-risk human papillomavirus (HR-HPV) in cervical tissue specimens is significant for cervical cancer prevention. A sensitive microplate fluorometric hybridization assay (MFHA) was designed for the detection of HPV DNA 16 and 18 in cervical tissue. Following optimization and validation of the method, 60 formalin-fixed and paraffin-embedded cervical samples representing different cervical intraepithelial neoplasia grades of HPV-associated lesions were tested to determine the sensitivity and specificity of the assay. Using consensus GP5+/6+ biotin-labeled primers to amplify a conserved region within the L1 gene, the amplicons were added to the microplate wells coated with specific probes for the hybridization of HPV 16 and 18 individually. Final detection was performed with streptavidin-AlexaFluor488 conjugated. The results were then compared with type-specific nested polymerase chain reaction (PCR) and colorimetric microplate assay. While the agreement between the results obtained by the type-specific nested PCR and fluorometric assay for the detection of both HR-HPV types was 100%, this agreement for the detection of HPV type 16 and 18 using microplate colorimetric assay was 94.2% and 85% respectively. Overall, the results of the fluorometric and colorimetric assays are promising for detecting both HR-HPV types in a large number of cervical tissue samples with the higher MFHA assay sensitivity.

1903 Esophageal Squamous Papilloma: A Rare Epithelial Tumor of Undetermined Significance

INTRODUCTION: Esophageal squamous papilloma (ESP) is an uncommon lesion with less than 200 cases described. Although typically a benign lesion, the etiology remains uncertain. Currently, no guidelines exist for the management of esophageal squamous papilloma. CASE DESCRIPTION/METHODS: A 59-year-old woman presented with dysphagia; she reported symptoms of acid reflux and globus sensation. One year prior, esophagogastroduodenoscopy (EGD) was performed for these symptoms and revealed atrophic changes consistent with gastritis. Biopsy at that time was negative for H. Pylori infection. She was treated with PPI therapy, however her symptoms persisted. She endorsed intermittent dysphagia but denied weight loss or poor appetite. Physical exam revealed no palpable thyromegaly or epigastric tenderness. Repeat upper EGD revealed a white, 7 mm frond-like pedunculated polyp located 20 cm from the incisors (Figure 1). Endoscopic ultrasound (EUS) was performed, the origin of the lesion appeared to be within the superficial mucosa. The endosonographic borders were well defined, intact interfaces between the mass and adjacent structures suggested a lack of submucosal invasion (Figure 2). No was lymphadenopathy seen. The polyp was excised endoscopically (Figure 3), pathological review identified the specimen as an esophageal squamous papilloma, positive for Ki67 and HPV marker P16. The patient tolerated the procedure well and had no recurrence of symptoms after polypectomy. DISCUSSION: Often an incidental finding on endoscopy, ESP are most commonly found in adults over age 50 and typically involve the middle and distal thirds of the esophagus. ESP may be associated with dyspepsia but rarely cause obstruction. Purported etiologies include mechanical, chemical and viral insult to mucosa but is likely multifactorial. The malignant potential of ESP remains uncertain; although rare, several reported cases have been complicated by carcinoma. Studies to detect HPV DNA in ESP show variable percentage of HPV positivity. If HPV infection predisposes to ESP, this may explain cases of malignant conversion as HPV is a known cause of squamous cell cancer. ESP should be considered in patients over 50 years old presenting with dysphagia or GERD resistant to medical therapy. We recommend early recognition and removal of esophageal squamous papilloma due to ambiguity regarding malignant potential.

Overexpression of p16INK4a Serves as Prognostic Marker in Squamous Cell Vulvar Cancer Patients Treated With Radiotherapy Irrespective of HPV-Status.

Purpose: We aimed to evaluate the impact of HPV-driven carcinogenesis on outcome in vulvar squamous cell carcinoma patients (VSCC) treated with radiotherapy.Methods and Materials: Analysis of clinical, pathological, and treatment data, HPV DNA-detection and -genotyping as well as p16INK4a immunohistochemistry were performed in 75 VSCC patients. Kaplan–Meier-method was used to estimate locoregional control (LC), Progression-free survival (PFS), and Overall Survival (OS). Univariate survival time comparisons were performed using the log-rank-test. Chi-square/Fisher exact test was used to assess correlations between HPV DNA and p16INK4a data, pathological, clinical, and treatment characteristics.Results: 23/75 (30.67%) of all women had locoregional relapse, 7/75 (9.3%) systemic recurrence, and 35/75 (46.67%) died after a median follow-up of 26.4 months. 21.3% of the tumors were HPV DNA-positive, mostly (93.75%) for the high-risk (HR) HPV type 16. 25.3% showed p16INK4a-overexpression. 17.3% showed concomitant HPV DNA- and p16INK4a-positivity (cHPPVC). Patients with p16INK4a-overexpression, irrespective of the HPV DNA status, showed significantly better PFS (5-year-PFS 69.3 vs. 39.2%, p = 0.045), LC (5-year-LC 86.7 vs. 56.7%, p = 0.033) and a strong trend for better OS (5-year-OS 75.6 vs. 43.9%, p = 0.077). Patients with cHPPVC showed a trend for better PFS (5-year-PFS 72.7 vs. 41.3%, p = 0.082) and OS (5-year-OS 81.1 vs. 45.7%, p = 0.084) but no significant benefit for LC.Conclusions: Patients with cHPPVC, indicating an etiological relevance of HPV in the respective tumors, showed a better, albeit not significant, prognosis. The sole detection of p16INK4a-overexpression is a prognostic factor for survival in vulvar cancer and indicates better prognosis after radiotherapy, independent of detection of HPV DNA. p16INK4a should be used as surrogate marker for HPV-driven carcinogenesis in vulvar cancer with caution.

Human papillomavirus as an independent risk factor of invasive cervical and endometrial carcinomas in Jordan

BackgroundEndometrial and cervical carcinomas are the most common gynecologic malignancies in Western world and many countries. The human papillomavirus (HPV) high-risk genotypes are associated with cervical carcinoma (CC). Chlamydia trachomatis (C. trachomatis), the most common sexually transmitted bacterial infection worldwide, considered a cofactor for HPV infection and CC. Information on HPV infection rate and type distribution among Jordanian women having CC is currently limited and unavailable among those with endometrial carcinoma. Therefore, the present study aimed to provide an updated estimate on HPV infection rate and its high-risk genotypes' distribution among Jordanian women by comparing data from invasive cervical carcinoma (ICC) to normal cervical tissues. Similarly, assessment of HPV infection rate was extended to the endometrial tissues. C. trachomatis infection was investigated as well to explore its possibility as HPV cofactor for induction of such carcinomas. MethodsTotal DNA was extracted from 144 formaldehyde-fixed paraffin-embedded cervical and endometrial tissue, equally divided between age-matched control and carcinoma cases. Polymerase chain reaction (PCR) was used for general detection of HPV-DNA, high risk HPV-16 and 18 genotypes and C. trachomatis DNA using specific primers. ResultsHPV infection was detected in 91.7% and 61.1% of cervical cancer patients and controls, respectively. Likewise, it was higher among cases (47.2%) than controls (13.8%) in endometrial biopsies. Significantly higher HPV infection rates were found among ICC and endometrial control biopsies of women >50 years. Out of 33 HPV positive ICC cases, single HPV-16 infections were detected in 69.7% compared to HPV-18 (15.2%), while HPV-16/18 co-infections were only found in three (9%) samples. C. trachomatis was not detected in all studied groups. ConclusionThe present study has successfully provided an updated estimate on HPV infection rate among Jordanian women with and without ICC and endometrial carcinoma. In addition, a lack of co-infection was observed between HPV and C. trachomatis in both cancer types.

HPV-negative tumors of the uterine cervix

Human papillomaviruses (HPV) are the causative agents of virtually all cervical carcinomas. Nevertheless, a small proportion of cervical cancer are negative for HPV, although the significance of this finding remains unclear. We aimed to provide insight into the differential clinico-pathological characteristics of this unusual subset of HPV-negative cervical cancer. We performed HPV-DNA detection using a highly sensitive PCR test (SPF10) and p16 immunostaining in 214 cervical carcinomas specimens from women treated at the Gynecological Oncology Unit of the Hospital Clinic (Barcelona, Spain) from 2012 to 2015. The clinical and pathological characteristics, including disease-free survival and overall survival, of HPV-negative and -positive cervical carcinomas were compared. Twenty-one out of 214 tumors (10%) were negative for HPV DNA. HPV-negative tumors were more frequently of the non-squamous type (9/21, 43% vs. 37/193, 19%; p < 0.01) and showed negative p16 staining (9/21; 43% vs. 7/193; 4%; p < 0.01). HPV-negative tumors were more frequently diagnosed at advanced FIGO stage (19/21, 91% vs. 110/193, 57%; p < 0.01) and more frequently had lymph node metastases (14/21, 67% vs. 69/193, 36%; p < 0.01). Patients with HPV-negative cervical cancer had a significantly worse disease-free survival (59.8 months, 95% confidence interval 32.0–87.6 vs. 132.2 months, 95% confidence interval 118.6–145.8; p < 0.01) and overall survival (77.0 months, 95% confidence interval 47.2–106.8 vs. 153.8 months, 95% confidence interval 142.0–165.6; p = 0.01) than women with HPV-positive tumors. However, only advanced FIGO stage and lymph node metastases remained associated with a poor disease-free survival and overall survival on multivariate analysis. In conclusion, our results suggest that a low percentage of cervical cancer arise via an HPV-independent pathway. These HPV-negative tumors are diagnosed at advanced stages, show higher prevalence of lymph nodes metastases and have an impaired prognosis.

Human papillomavirus DNA detected in fingertip, oral and bathroom samples from unvaccinated adolescent girls in Tanzania

ObjectiveHuman papillomavirus (HPV) DNA has been detected in vaginal samples from adolescent girls who report no previous sex and, in high-income settings, from fingertips, raising the possibility of non-sexual transmission....

Correlates of Human Papillomavirus Vaccination and Association with HPV-16 and HPV-18 DNA Detection in Young Women.

Background: Despite a reduction in the prevalence of vaccine-preventable types of human papillomavirus (HPV), attributed to increased HPV vaccine uptake, HPV continues to be a major cause of cancer in the United States. Methods: We assessed factors associated with self-reported HPV vaccine uptake, HPV vaccination effectiveness, using DNA testing to assess HPV types 16 and/or 18 (HPV 16/18) positivity, and patterns of HPV vaccination in 375 women aged 21-29 years who were eligible to receive catch-up vaccination, using baseline data collected from March 2012 to December 2014 from a randomized controlled trial evaluating a novel approach to cervical cancer screening. Results: More than half (n = 228, 60.8%) of participants reported receipt of at least one HPV vaccine dose and 16 (4.3%) tested positive for HPV 16/18 at baseline. College-educated participants were four times more likely to have been vaccinated than those reporting high school education or less. 56.5% of HPV-vaccinated participants reported first dose after age 18 and 68.4% after first vaginal intercourse. Women vaccinated after age 18 and women vaccinated after first vaginal intercourse were somewhat more likely to be infected with HPV 16/18 infection compared with women vaccinated earlier, but these associations did not reach statistical significance. Conclusions: HPV vaccination is common among college-educated women in the catch-up population but less common among those without college education. Contrary to current guidelines, catch-up females frequently obtain HPV vaccination after age 18 and first vaginal intercourse. Women without a college education represent an ideal population for targeted HPV vaccination efforts that emphasize vaccination before sexual debut.

High rate of detection of ultrasound signs of prostatitis in patients with HPV-DNA persistence on semen: role of ultrasound in HPV-related male accessory gland infection.

Papillomavirus (HPV) often occurs in the semen of patients with male accessory gland infection (MAGI). Ultrasound (US) evaluation has been suggested as a promising diagnostic tool for patients with HPV-related MAGI. No data on the spontaneous clearance of HPV-DNA have been reported so far in HPV-related MAGI. The primary aim of the study was to assess the percentage of early HPV-DNA spontaneous clearance in patients with prostatitis. The secondary aim was to evaluate the frequency of spontaneous clearance of HPV-DNA among patients with prostatitis associated with the presence or absence of US abnormalities. Patients with inflammatory MAGI and at least one suspicious criterion for HPV infection underwent semen HPV-DNA detection and prostate US. The presence of HPV-DNA was further investigated after a 6-month-long follow-up. Eighty patients satisfied the inclusion criteria and were recruited in the study. 69% of patients (55/80) showed HPV-DNA persistence in the semen. Among them, 82% (45/55) was positive for US signs of prostatitis, while they occurred only in 12% (3/25) of those patients with no sign of HPV-DNA persistence (p < 0.001). All patients with persistent high-risk HPV genotype (n = 30) showed at least two US signs of prostatitis. In 73% of patients (22/30), E6 and E7 mRNAs were detected. US signs of prostatitis more frequently occurred in patients with evidence of HPV-DNA persistence on semen, especially in those with high-risk genotypes. This highlights the importance of US in the framework of HPV-related MAGI.

Cervical Human Papillomavirus Prevalence, Genotypes, and Associated Risk Factors among Female Sex Workers in Greater Accra, Ghana.

Cervical cancer is a largely preventable disease mediated by persistent infection with high-risk Human Papillomaviruses (Hr-HPV). There are now three approved vaccines against the most common HPV genotypes. In Ghana, mortality due to cervical cancer is on the rise, due to the absence of an organized and effective cervical cancer prevention and control program. Data on circulating HPV genotypes is important for studying the likely impact of mass introduction of HPV vaccination of the female population before sexual debut. High HPV prevalence has been reported in Female Sex Workers (FSWs), who constitute an important active group for maintenance of HPV in the population. This study was conducted to determine the size of HPV prevalence in this group and to provide information for future assessment of the impact of vaccine introduction in the country. We conducted a cross-sectional study where the snowballing technique was used to identify and select FSW's ≥18 years, operating within suburbs of Greater Accra Region (GAR). A risk factor assessment interview was conducted and cervical swabs were collected for HPV-DNA detection and genotyping by Nested Multiplex PCR. Hundred participants, age ranging from 18 to 45 years, median 24 years, were studied. The prevalence of Cervical HPV was 26%. Eleven genotypes were detected comprising 9 high-risk in order of decreasing prevalence HPV-16 (8%), HPV-35 (5%), HPV-33/39/-68 (3%), HPV-52/51/59 (2%) and HPV-18 (1%) and 2 Low-risk types, HPV-42(3%), and HPV-43 (1%). Three women had HPV types that could not be genotyped by our method. Oral contraceptives use was associated with a reduced chance of HPV infection (P=0.002; OR=0.19, 95% CI 0.07-0.54). This study found a high HPV prevalence among FSWs in the GAR. A high number of Hr-HPV genotypes seen are vaccine preventable, providing additional compelling argument for implementing a national cervical cancer prevention plan including vaccination.

Accuracy of high-risk HPV DNA detection from urine and cervical samples in abnormal pap smear women

Accuracy of high-risk HPV DNA detection from urine and cervical samples in abnormal pap smear women